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Nd 2Institute of Microbiology, Division of Biology, ETH Z ich

Possibly Title Loaded From File Brucella may aid teach us the function of your typical prion protein (1). In Watarai's (1) experiments, each wild-type and VirB-deficient bugs are avirulent in PrPC-deficient mice. Hence, the Hsp60 rPC connection is very important in true infections (Fig. 1). So, what can Brucella teach us about PrPC The prion would be the infectious agent causing transmissible spongiform encephalopathies (14).Nd 2Institute of Microbiology, Division of Biology, ETH Z ich, CH-8092 Z ich, SwitzerlandAren't bugs a source of continuous amazement Consider, by way of example, how cunningly bacteria conspire to shanghai the molecular machines of their mammalian hosts for their own objectives. In addition to serving the bugs, this evil intelligence is exploitable for studying cellular physiology, and also the bewildering affinity of bacterial toxins for important host cell proteins has taught us many a thing on how cells operate. Perhaps Brucella may possibly support teach us the function with the regular prion protein (1). Brucella species are Gram-negative facultative intracellular pathogens. They invade, resist intracellular killing, and replicate in phagocytic and nonphagocytic cells (two). But how does Brucella initiate replication in macrophages The make contact with together with the bug instructs the macrophage to internalize it; the mode of internalization (Fc and complement receptors vs. uptake of nonopsonized bugs) determines the fate of your bug (2). Brucella actively modulates its personal engulfment. It induces peculiar membrane ruffles at its web site of make contact with with all the macrophage and slow "swimming internalization" into a macropinosome. Then, Brucella takes complete handle from the macropinosome. It inhibits its maturation into a degradative lysosome (three) and reprograms it to obtain endoplasmic reticulum markers and mature into a "replicative phagosome" where bacteria start multiplying (Fig. 1; reference two). For playing these tricks, Brucella relies on a set of virulence factors, which includes a bacterial injection organelle termed VirB or sort IV secretion system (4). When exposed to macrophages in vitro, virB-deficient bugs can't modulate phagocytosis and are degraded in the lysosome. But what does the VirB method exactly do in this context As outlined by Watarai et al. (1), it may be necessary for transporting the bacterial heat shock protein Hsp60 onto the surface of the bug. Unexpectedly, the chaperonin Hsp60, which ordinarily hangs out in the cytoplasm and bargains with unfolded proteins (9), turns out to reside on the surface of wild-type Brucella abortus but not virB mutants.Address correspondence to Adriano Aguzzi, Institute of Neuropathology, Department of Pathology, University Hospital of Z ich, Schmelzbergstr. 12, CH-8091 Z ich, Switzerland. Phone: 41-1-255-2869; Fax: 41-1255-4402; E-mail: adriano@pathol.unizh.chOn the macrophage surface, Brucella attaches to cholesterol-rich microdomains known as lipid "rafts" (102). There, Hsp60 appears to snatch at an unlikely buddy, the cellular prion protein (PrPC), which can be encoded by the Prnp gene and resides preferentially in rafts. PrPC is apparently recruited to the macrophage's membrane protrusions, which engulf the bacteria, and subsequently to the early macropinosome. In Prnpo/o macrophages, B. abortus does not modulate phagocytosis nor phagosome maturation. This can be strikingly related for the behavior of Brucella virB mutants and suggests that the Hsp60 rPC interaction is instrumental for these actions. The latter presumption is backed up by animal studies.
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